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Regulatory Science Framework for Nano(bio)material-based Medical Products and Devices

Deliverables

First beta version DSS

We will arrange a workshop where approximately 20-25 stakeholders (regulators, industry, academia) are invited to inspect and interact with the early version of the DSS, including example data sets for input. This will give valuable feedback on adjustments of the DSS to users' needs and wishes.

Knowledge-HUB (K-HUB: Social media strategy implementation, explicit knowledge sharing repository)

This online platform should provide access to all non-confidential REFINE results. The platform should be searchable and allow filtering, contributions and -if deemed useful- opportunities to engage in online discussions. We will make use of the glossary of terminology to appeal to various stakeholder communities.

DSS stakeholder interaction workshop

We will arrange a workshop where approximately 20-25 stakeholders (regulators, industry, academia) are invited to inspect and interact with the early version of the DSS, including example data sets for input. This will give valuable feedback on adjustments of the DSS to users' needs and wishes.

Two workshops with strong participation from regulators

Two workshops will be organised with at least 15 external participants each, from regulatory bodies and expert-level scientific committees related to regulatory bodies, plus additional high-level participants from research and development.

Reflection Document

A reflection document will present the outline of the methodology to design intelligent testing strategies, considerations regarding populating the repository and ranking methods according to product and measurand, current observations on CQAs, as well as approaches and structures intended for the DSS. This document will serve both as an internal orientation and as a foundation for interaction with external stakeholders as it will feed into the whitepaper-drafting in WP1.

First draft of whitepaper

The draft whitepaper will propose a catalogue of information requirements and needs for harmonisation (e.g. to address borderline products that fall under different legislature in different world regions). It will propose a gap analysis, where scientific state of the art and regulatory practice seem out of step (e.g. present a list of major adversities of administered NBMs described in the scientific literature, that are hard to predict by current standard testing methods). Thirdly the document will propose a heuristic how to assimilate new evidence in reliable and efficient way into regulatory strategies (e.g. which testing methods would deliver information that supports the modeling of an NMB-specific Adverse Outcome Pathway, for example for CARPA ).

Report on in vitro characterization of nanoparticle distribution

Report on the quantitative evaluation of key variables such as apparent permeability through various barriers systems, or uptake kinetics in key cell populations

Publications

Delivery of oligonucleotide-based therapeutics: challenges and opportunities.

Author(s): Suzan M. Hammond; Annemieke Aartsma-Rus; Sandra Alves; Sven Even F. Borgos; Ronald A.M. Buijsen; Rob W.J. Collin; Giuseppina Covello; Giuseppina Covello; Michela A. Denti; Lourdes R. Desviat; Lucia Echevarria; Camilla Foged; Gisela Gaina; Alejandro Garanto; Aurélie Goyenvalle; Magdalena Guzowska; Irina Holodnuka; David R. Jones; Sabine Krause; Taavi Lehto; Taavi Lehto; Marisol Montolio; Willeke M
Published in: Hammond , S M , Aartsma-Rus , A , Alves , S , Borgos , S E , Buijsen , R A M , Collin , R W J , Covello , G , Denti , M A , Desviat , L R , Echevarría , L , Foged , C , Gaina , G , Garanto , A , Goyenvalle , A T , Guzowska , M , Holodnuka , I , Jones , D R , Krause , S , Lehto , T , Montolio , M , Van Roon-Mom , W & Arechavala-Gomeza , V 2021 , ' Delivery of oligonucleotide-based therapeutics : c, 8, 2021, ISSN 1757-4676
Publisher: John Wiley & Sons Ltd.
DOI: 10.15252/emmm.202013243

Pharmacokinetic modelling to estimate intracellular favipiravir ribofuranosyl-5'-triphosphate exposure to support posology for SARS-CoV-2

Author(s): Henry Pertinez; Rajith K. R. Rajoli; Saye Khoo; Andrew Owen
Published in: Journal of Antimicrobial Chemotherapy, 1, 2021, ISSN 0305-7453
Publisher: Oxford University Press
DOI: 10.1101/2021.01.03.21249159

Preclinical Development of Orally Inhaled Drugs (OIDs)-Are Animal Models Predictive or Shall We Move Towards In Vitro Non-Animal Models?

Author(s): Dania Movia; Adriele Prina-Mello
Published in: Animals : an Open Access Journal from MDPI, 1, 2020, ISSN 2076-2615
Publisher: MDPI AG
DOI: 10.3390/ani10081259

Label-Free Digital Holographic Microscopy for In Vitro Cytotoxic Effect Quantification of Organic Nanoparticles

Author(s): Kai Moritz Eder, Anne Marzi, Álvaro Barroso, Steffi Ketelhut, Björn Kemper, and Jürgen Schnekenburger
Published in: Cells, 2022, ISSN 2073-4409
Publisher: MDPI
DOI: 10.3390/cells11040644

Dose Prediction for Repurposing Nitazoxanide in SARS-CoV-2 Treatment or Chemoprophylaxis

Author(s): Rajith K. R. Rajoli; Henry Pertinez; Usman Arshad; Helen Box; Lee Tatham; Paul Curley; Megan Neary; Joanne Sharp; Neill J. Liptrott; Anthony Valentijn; Christopher David; Steve P. Rannard; Ghaith Aljayyoussi; Shaun H. Pennington; Andrew Hill; Marta Boffito; Stephen A. Ward; Saye Khoo; Patrick G. Bray; Paul M. O'Neill; W. David Hong; Giancarlo A. Biagini; Andrew Owen
Published in: medRxiv, 9, 2021, ISSN 0306-5251
Publisher: Blackwell Publishing Inc.
DOI: 10.22541/au.158938595.50403411

A Substrate-Mimicking Basement Membrane Drives the Organization of Human Mesenchymal Stromal Cells and Endothelial Cells Into Perivascular Niche-Like Structures

Author(s): Perugini V., Santin M.
Published in: Frontiers in Cell and Developmental Biology, 2021, ISSN 2296-634X
Publisher: Frontiers Media S.A.
DOI: 10.3389/fcell.2021.701842

Endotoxin contamination of engineered nanomaterials: Overcoming the hurdles associated with endotoxin testing

Author(s): Hannon G., Prina-Mello A.
Published in: Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2021, ISSN 1939-5116
Publisher: John Wiley and Sons Inc
DOI: 10.1002/wnan.1738

Docetaxel gold complex nanoflowers: A chemo-biological evaluation for their use as nanotherapeutics.

Author(s): Maroua Ben Haddada; Dania Movia; Adriele Prina-Mello; Jolanda Spadavecchia
Published in: Colloids and Surfaces B: Biointerfaces, 6, 2020, ISSN 0927-7765
Publisher: Elsevier BV
DOI: 10.1016/j.colsurfb.2020.111172

Nano-enabled medicinal products: Time for an international advanced community?

Author(s): Gioria S., Caputo F., Mehn D.
Published in: Nanomedicine, 2019, ISSN 1743-5889
Publisher: Future Medicine Ltd.
DOI: 10.2217/nnm-2019-0173

An Open Label, Adaptive, Phase 1 Trial of High-Dose Oral Nitazoxanide in Healthy Volunteers: An Antiviral Candidate for SARS-CoV-2

Author(s): Walker L.E., FitzGerald R., Saunders G., Lyon R., Fisher M., Martin K., Eberhart I., Woods C., Ewings S., Hale C., Rajoli R.K.R., Else L., Dilly-Penchala S., Amara A., Lalloo D.G., Jacobs M., Pertinez H., Hatchard P., Waugh R., Lawrence M., Johnson L., Fines K., Reynolds H., Rowland T., Crook R., Okenyi E., Byrne K., Mozgunov P., Jaki T., Khoo S., Owen A., Griffiths G., Fletcher T.E., the AGILE pl
Published in: Clinical Pharmacology and Therapeutics, 2021, ISSN 0009-9236
Publisher: Nature Publishing Group
DOI: 10.1002/cpt.2463

Subcellular detection of PEBCA particles in macrophages: combining darkfield microscopy, confocal Raman microscopy, and ToF-SIMS analysis

Author(s): Antje Vennemann, Daniel Breitenstein, Elke Tallarek, Yrr Mørch, Ruth Schmid, Martin Wiemann
Published in: Drug Delivery and Translational Research, 2022, ISSN 2190-393X
Publisher: Springer Pub. Co.,
DOI: 10.1007/s13346-022-01128-3

Pre-clinical 2D and 3D toxicity response to a panel of nanomaterials; Comparative assessment of NBM-induced liver toxicity

Author(s): Melissa Anne Tutty, Adriele Prina-Mello, Gabriele Vella
Published in: Drug Delivery and Translational Research, 2022, ISSN 2190-393X
Publisher: Springer Pub. Co.,
DOI: 10.21203/rs.3.rs-1277778/v1

Immunotoxicity Considerations for Next Generation Cancer Nanomedicines

Author(s): Hannon, Gary; Lysaght, Joanne; Liptrott, Neill J.; Prina‐Mello, Adriele
Published in: Advanced Science, Vol 6, Iss 19, Pp n/a-n/a (2019), 4, 2019, ISSN 2198-3844
Publisher: John Wiley and Sons Inc.
DOI: 10.1002/advs.201900133

Towards more predictive, physiological and animal-free in vitro models: Advances in cell and tissue culture 2020 conference proceedings

Author(s): Singh B., Abdelgawad M.E., Ali Z., Bailey J., Budyn E., Civita P., Clift M.J.D., Connelly J.T., Constant S., Hittinger M., Kandarova H., Kearns V.R., Kiuru T., Kostrzewski T., Kress S., Durban V.M., Lehr C.-M., McMillan H., Metz J.K., Monteban V., Movia D., Neto C., Owen C., Paasonen L., Palmer K.A., Pilkington G.J., Pilkington K., Prina-Mello A., Roper C., Sheard J., Smith S., Turner J.E., Roy I.
Published in: ATLA Alternatives to Laboratory Animals, 2021, ISSN 0261-1929
Publisher: Fund for the Replacement of Animals in Medical Experiments
DOI: 10.1177/02611929211025006

Bridging communities in the field of nanomedicine.

Author(s): Halamoda-Kenzaoui, Blanka; Baconnier, Simon; Bastogne, Thierry; Bazile, Didier; Boisseau, Patrick; Borchard, Gerrit; Borgos, Sven Even; Calzolai, Luigi; Cederbrant, Karin; Di Felice, Gabriella; Di Francesco, Tiziana; Dobrovolskaia, Marina A.; Gaspar, Rogério; Gracia, Belén; Hackley, Vincent A.; Leyens, Lada; Liptrott, Neill; Park, Margriet; Patri, Anil; Roebben, Gert; Roesslein, Matthias; Thürm
Published in: Regulatory Toxicology and Pharmacology, 3, 2019, ISSN 0273-2300
Publisher: Academic Press
DOI: 10.1016/j.yrtph.2019.04.011

Launching stakeholder discussions on identified regulatory needs for nanotechnology-enabled health products

Author(s): B. HALAMODA-KENZAOUI, H. BOX, M. VAN ELK, S. GAITAN, R. GEERTSMA, E. GAINZA LAFUENTE, A. OWEN, A. DEL POZO, M. ROESSLEIN, S. BREMER- HOFFMANN
Published in: Precision Nanomedicine, 2020, ISSN 2639-9431
Publisher: Andover House
DOI: 10.33218/001c.13521

Measuring particle size distribution and mass concentration of nanoplastics and microplastics: addressing some analytical challenges in the sub-micron size range

Author(s): Caputo F., Vogel R., Savage J., Vella G., Law A., Della Camera G., Hannon G., Peacock B., Mehn D., Ponti J., Geiss O., Aubert D., Prina-Mello A., Calzolai L.
Published in: Journal of Colloid and Interface Science, 2021, ISSN 0021-9797
Publisher: Academic Press
DOI: 10.1016/j.jcis.2020.12.039

A comparative in vitro study of the effect of biospecific integrin recognition processes and substrate nanostructure on stem cell 3D spheroid formation

Author(s): Valeria Perugini; Matteo Santin
Published in: Journal of Materials Science. Materials in Medicine, 3, 2020, ISSN 1573-4838
Publisher: Springer Nature
DOI: 10.1007/s10856-020-06373-x

Development of scaffold-free vascularized pancreatic beta-islets in vitro models by the anchoring of cell lines to a bioligand-functionalized gelatine substrate

Author(s): Valeria Perugini, Samuel M. Flaherty, Matteo Santin
Published in: Journal of Materials Science: Materials in Medicine, 2022, Page(s) 33:37, ISSN 2190-393X
Publisher: Springer Pub. Co.,
DOI: 10.1007/s10856-022-06658-3

Toward Consensus on Correct Interpretation of Protein Binding in Plasma and Other Biological Matrices for COVID-19 Therapeutic Development

Author(s): Boffito M., Back D.J., Flexner C., Sjö P., Blaschke T.F., Horby P.W., Cattaneo D., Acosta E.P., Anderson P., Owen A.
Published in: Clinical Pharmacology and Therapeutics, 2021, ISSN 0009-9236
Publisher: Nature Publishing Group
DOI: 10.1002/cpt.2099

Biophysical Characterization of Viral and Lipid-Based Vectors for Vaccines and Therapeutics with Light Scattering and Calorimetric Techniques

Author(s): Markova N., Cairns S., Jankevics-Jones H., Kaszuba M., Caputo F., Parot J.
Published in: Vaccines, 2021, ISSN 2076-393X
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/vaccines10010049

Shutting the gate before the horse has bolted: is it time for a conversation about SARS-CoV-2 and antiviral drug resistance?

Author(s): Julian A. Hiscox; Julian A. Hiscox; Saye Khoo; James P. Stewart; Andrew Owen
Published in: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2, 2021, ISSN 0305-7453
Publisher: Oxford University Press
DOI: 10.1093/jac/dkab189

Improved multidetector asymmetrical-flow field-flow fractionation method for particle sizing and concentration measurements of lipid-based nanocarriers for RNA delivery

Author(s): Mildner R., Hak S., Parot J., Hyldbakk A., Borgos S.E., Some D., Johann C., Caputo F.
Published in: European Journal of Pharmaceutics and Biopharmaceutics, 2021, ISSN 0939-6411
Publisher: Elsevier BV
DOI: 10.1016/j.ejpb.2021.03.004

Decision support system for preclinical assessment of nano/biomaterials used in the medical sector: the REFINE DSS

Author(s): Alex Zabeo, Fabio Rosada, Lisa Pizzol, Fanny Caputo, Sven Even Borgos, Jeremie Parot, Robert E Geertsma, Joost Jacob Pouw, Rob J Vandebriel, Oihane Ibarrola Moreno, Danail Hristozov
Published in: Drug Delivery and Translational Research, 2022, ISSN 2190-393X
Publisher: Springer Pub. Co.,
DOI: 10.21203/rs.3.rs-1246960/v1

Measuring particle concentration of multimodal synthetic reference materials and extracellular vesicles with orthogonal techniques: Who is up to the challenge?

Author(s): Robert Vogel; John Savage; Julien Muzard; Giacomo Della Camera; Gabriele Vella; Alice Law; Marianne Marchioni; Dora Mehn; Otmar Geiss; Ben Peacock; Dimitri Aubert; Luigi Calzolai; Fanny Caputo; Adriele Prina-Mello
Published in: Journal of Extracellular Vesicles, Vol 10, Iss 3, Pp n/a-n/a (2021), 8, 2021, ISSN 2001-3078
Publisher: John Wiley and Sons Inc
DOI: 10.1002/jev2.12052

Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics

Author(s): Arshad U., Pertinez H., Box H., Tatham L., Rajoli R.K.R., Curley P., Neary M., Sharp J., Liptrott N.J., Valentijn A., David C., Rannard S.P., O’Neill P.M., Aljayyoussi G., Pennington S.H., Ward S.A., Hill A., Back D.J., Khoo S.H., Bray P.G., Biagini G.A., Owen A.
Published in: Clinical Pharmacology and Therapeutics, 2020, ISSN 0009-9236
Publisher: Nature Publishing Group
DOI: 10.1002/cpt.1909

Methodological needs in the quality and safety characterisation of nanotechnology-based health products: Priorities for method development and standardisation

Author(s): B. Halamoda-Kenzaoui, R.J. Vandebriel, A. Howarth, M. Siccardi, C.A.W. David, N.J. Liptrott, M. Santin, S.E. Borgos, S. Bremer-Hoffmann, F. Caputo
Published in: Journal of Controlled Release, 336, 2021, Page(s) 192-206, ISSN 0168-3659
Publisher: Elsevier BV
DOI: 10.1016/j.jconrel.2021.06.016

A Multi-step In Vitro Hemocompatibility Testing Protocol Recapitulation the Foregn Body Reaction to Nanocarriers

Author(s): Valeria Perugini, Ruth Schmid, Yrr Mørch, Isabelle Texier, Martin Brodde, Matteo Santin
Published in: Drug Delivery and Translational Research, 2022, ISSN 2190-393X
Publisher: Springer Pub. Co.,
DOI: 10.1007/s13346-022-01141-6

Organoid Formation Driven by Synthetic Biomaterials Mimicking the Basement Membrane

Author(s): Valeria Perugini, Matteo Santin
Published in: Chinese-European Societies for Biomaterials Conference, 2019
Publisher: Chinese Society for Biomaterials (CSBM) and European Society for Biomaterials (ESB)

Medical nanoparticle impact on macrophage temporal dry mass development quantified in vitro by digital holographic microscopy

Author(s): Kai Eder, Anne Marzi, Álvaro Barroso, Björn Kemper, Jürgen Schnekenburger
Published in: Quantitative Phase Imaging VII; 116531Q, Proceedings Volume 11653, 2021
Publisher: SPIE
DOI: 10.1117/12.2577655

Perivascular Niche Based on Hyperbranched Laminin Dendron as a New Feasible Approach to Ameliorate Stemness Deprivation During In Vitro Expansion

Author(s): Valeria Perugini, Matteo Santin
Published in: 30th European Society for Biomaterials Conference, 2019, Page(s) III-OS10-05 page 188
Publisher: European Society for Biomaterials

Label-free in vitro quantification of medical nanoparticle effects on macrophages with digital holographic microscopy

Author(s): Kai Moritz Eder, Anne Marzi, Alvaro Barroso, Björn Kemper, and Jürgen Schnekenburger
Published in: Imaging and Applied Optics Congress, OSA Technical Digest, Imaging and Applied Optics Congress, OSA Technical Digest (Optica Publishing Group, 2020), paper JW5A.4., 2020
Publisher: OSA

Automated detection of macrophages in quantitative phase images by deep learning using a mask region-based convolutional neural network

Author(s): Kai Eder, Tobias Kutscher, Anne Marzi, Álvaro Barroso, Jürgen Schnekenburger, Björn Kemper
Published in: Label-free Biomedical Imaging and Sensing, 2021
Publisher: SPIE
DOI: 10.1117/12.2577232

Cell Detection and Segmentation in Quantitative Digital Holographic Phase Contrast Images Utilizing a Mask Region-based Convolutional Neural Network

Author(s): Tobias Kutscher, Kai Eder, Anne Marzi, Álvaro Barroso, Jürgen Schnekenburger, and Björn Kemper
Published in: OSA Optical Sensors and Sensing Congress 2021, OSA Technical Digest (Optica Publishing Group, 2021), paper JTu5A.23., 2021
Publisher: OSA

Synthetic Basement Membrane Analogues Induce the formation of 3D Tissue-like Structures in 2D Cultures

Author(s): Matteo Santin (Invited Keynote Speaker)
Published in: Tissue Engineering and Regenerative Medicine International Societies (TERMIS) 2019, 2019, Page(s) 726
Publisher: TERMIS

Reduction of the influence of parasitic interferences and coherence induced disturbances in digital holography-based quantitative phase microscopy by modulation of the object illumination with an electrically focus tunable lens

Author(s): Kemper B., Barroso Á., Eder K., Marzi A., Ritz S., Schnekenburger J., Ketelhut S.
Published in: 2021
Publisher: Progress in Biomedical Optics and Imaging - Proceedings of SPIE
DOI: 10.1117/12.2577807

Enhanced quantitative phase imaging in Mach-Zehnder interferometer-based digital holographic microscopy by modulation of the object illumination with an electrically focus tunable lens

Author(s): Björn Kemper, Álvaro Barroso, Kai Eder, Anne Marzi, Sabrina Ritz, Angelos Ntovas, Jürgen Schnekenbürger, Steffi Ketelhut
Published in: Proceedings Volume 11786, Optical Methods for Inspection, Characterization, and Imaging of Biomaterials V; 117860I (2021), SPIE Optical Metrology, 2021, 2021
Publisher: SPIE
DOI: 10.1117/12.2592534

Cytotoxicity of Medical Nanoparticles and Effects on Cell Dry Mass Dynamics Quantified in vitro by Digital Holographic Microscopy

Author(s): Kai Moritz Eder
Published in: 2021
Publisher: XXX

Nanomedicinal products: An integrated approach for immunotoxicity testing

Author(s): Christina Giannakou
Published in: 2019
Publisher: Maastricht University

Editorial to Special Issue

Author(s): Kathleen Spring, Klaus-Michael Weltring, Adriele Prina-Mello, Ruth Schmid
Published in: Drug Delivery and Translational Research, 2022, ISSN 2190-393X
Publisher: Springer Pub. Co.,

Anticipation of regulatory needs for nanotechnology-enabled health products

Author(s): B. HALAMODA-KENZAOUI, H. BOX, M. VAN ELK, S. GAITAN, R. GEERTSMA, E. GAINZA LAFUENTE, A. OWEN, A. DEL POZO, M. ROESSLEIN, S. BREMER- HOFFMANN
Published in: 2019, ISSN 1831-9424
Publisher: Publications Office of the European Union
DOI: 10.2760/596822